The proposed studies are concerned with the pathogenesis and control of arteriosclerosis, and they are based upon the hypothesis that this lesion is the consequence of endothelial injury. Several lines of investigation will be undertaken, including the following: 1. The response of the rabbit artery to injury will be followed with particular attention to the junctional region between re-endothelialization and smooth muscle coverage. Additionally, the healing of de-endothelialized veins will be compared to that of arteries. 2. Estradiol has been found to express the hyperplasia that follows surgical repair in the rabbit aorta. To study the mechanism of this response and also to screen different compounds, tissue culture of medial smooth muscle cells will be undertaken. 3. Studies will be continued concerning identification of thrombogenic and inhibitory compounds of the subendothelium. The platelet reactivity of human umbilical vein following digestion with various specific enzymes will be correlated with the residual structures, as seen by electron microscopy. The nature of recently identified inhibitory extracts will be explored. 4. The platelet contractile apparatus, particularly that associated with membranes, will be evaluated for its relationship to responses with those connective tissues found in the subendothelium. BIBLIOGRAPHIC REFERENCES: Spaet, T.H., Stemerman, M.B., Veith, F.J. and Lejnieks, I.: Intimal injury and regrowth in the rabbit aorta: Medial smooth muscle cells as a source of neo-intima. Circ. Res. 36:58, 1975; Spaet, T.H., Gaynor, E. and Stemerman, M.B.: Thrombosis, atherosclerosis and endothelium. Am. Heart J. 87:661, 1974.